22P - Predictive value of Tertiary Lymphoid Structure in patients with mismatch repair deficient advanced/ recurrent endometrial cancer treated with Dostarlimab.

Background

In the phase 1 GARNET study, Dostarlimab (Dmab) a PD-1 inhibitor, demonstrated clinically meaningful and durable antitumor activity in patients (pts) with advanced/ metastatic mismatch repair deficient endometrial cancer (Adv MMRd EC) after chemotherapy (chemo). Recently, the RUBY trial showed a significant improvement in progression-free survival (PFS) with Dmab plus chemo vs chemo alone, changing the standard of care in the first-line setting of Adv MMRd EC. To date, there are no validated predictive biomarkers of response to Dmab. There is growing evidence that tertiary lymphoid structure (TLS) could be predictive of response and prognostic in early EC. In our pilot study, we aim to determine the predictive value of TLS in Adv MMRd EC.

Methods

Pts with Adv MMRd EC treated with Dmab as a second-line after chemo in GARNET and the French early access program at Institut Paoli-Calmettes were included. Tissue samples from hysterectomy, endometrial or metastasis biopsies were collected. Microscopic examination was performed using paraffin-embedded tissue blocks on HES-stained sections. The presence of TLS was defined by histomorphological and phenotypic (immunohistochemistry) criterias: a dense nodule of more than 200 closely grouped lymphoid cells, with an occasional germinal center; a mixture of CD20+ B cells forming a follicle and surrounded by CD3+ T cells. Mature TLS were defined by the presence of follicular dendritic cells CD23+, CD21+, L1CAM+.

Results

14 pts were included from 12/2017-10/2021. One patient was excluded (tissue sample not evaluable). 11/13 (84%) pts had endometrioid EC. TLS were identified in 6/13 (46%) pts (TLS+) on HES sections. Immunohistochemistry staining confirmed the diagnosis of TLS, but did not detect further TLS. Median PFS : 9 months in pts with TLS vs 3.5 months in pts with no TLS.

Conclusions

Presence of TLS on HES sections seemed associated with better PFS in Adv MMRd EC pts treated with second-line Dmab. HES seemed sufficient to identify TLS, and could in routine practice, help better select MMRd pts that could benefit from Dmab alone. Larger cohorts are required to confirm our observations and explore predictive factors of reponse to Dmab in first-line.

Legal entity responsible for the study

Institut Paoli-Calmettes.

Funding

Has not received any funding.

Disclosure

M. Kfoury: Financial Interests, Personal, Invited Speaker: AZ, GSK. F. Rousseau: Financial Interests, Personal, Financially compensated role: Eisai; Financial Interests, Personal, Other: Viatris. R. Sabatier: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Invited Speaker: Eisai, Clovis Oncology; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Personal, Other, Travel fees: MSD, Novartis; Non-Financial Interests, Personal, Other, Congress fees: GSK. All other authors have declared no conflicts of interest.